Hypertension exacerbates cerebrovascular oxidative stress induced by mild traumatic brain injury : protective effects of the mitochondria-targeted antioxidative peptide SS-31

Czigler, Andras [Czigler, András (Általános orvos), author] Department of Neurosurgery (UP / UPMS); Szentágothai Research Center (UP); Institute for Translational Medicine (UP / UPMS); Toth, Luca [Tóth, Luca (Idegsebészet), author] Department of Neurosurgery (UP / UPMS); Szentágothai Research Center (UP); Institute for Translational Medicine (UP / UPMS); Szarka, Nikolett [Szarka, Nikolett (Idegtudomány, agy...), author] Institute for Translational Medicine (UP / UPMS); Berta, Gergely [Berta, Gergely (Orvosi biológia), author] Orvosi Biológiai Intézet és Központi Elektronmi... (UP / UPMS); Amrein, Krisztina [Amrein, Krisztina (PhD Orvostudomány), author] Department of Neurosurgery (UP / UPMS); Neurotrauma Research Group (UP / SZRC); Czeiter, Endre [Czeiter, Endre (Idegsebészet), author] Department of Neurosurgery (UP / UPMS); Department of Immunology and Biotechnology (UP / UPMS); Neurotrauma Research Group (UP / SZRC); Lendvai-Emmert, Dominika [Lendvai-Emmert, Dominika (Egészségtudomány), author] Department of Neurosurgery (UP / UPMS); Szentágothai Research Center (UP); Bodó, Kornélia [Bodó, Kornélia (Immunológia, sejt...), author] Department of Immunology and Biotechnology (UP / UPMS); Tarantini, Stefano; Koller, Akos [Koller, Ákos (Szív és vérkeringés), author] Department of Neurosurgery (UP / UPMS); Department of Morphology and Physiology (SU / FHS); Circulation Research Laboratory (UP / SZRC); Testnevelési Egyetem; Sportgenetikai és Sportgerontológiai Kutató Cso... (TE / TTI); Ungvari, Zoltan [Ungvári, Zoltán István (Orvostudomány, él...), author]; Buki, Andras [Büki, András (Idegsebészet, ide...), author] Department of Neurosurgery (UP / UPMS); Neurotrauma Research Group (UP / SZRC); Toth, Peter [Tóth, Péter József (Idegsebészet, cer...), author] Department of Neurosurgery (UP / UPMS); MTA-PTE Clinical Neuroscience MR Research Group (UP / RG); Institute for Translational Medicine (UP / UPMS); Neurotrauma Research Group (UP / SZRC)

English Scientific Article (Journal Article)
Published: JOURNAL OF NEUROTRAUMA 0897-7151 36 (23) pp. 3309-3315 2019
  • SJR Scopus - Neurology (clinical): Q1
Identifiers
Traumatic brain injury (TBI) induces cerebrovascular oxidative stress, which is associated with neurovascular uncoupling, autoregulatory dysfunction and persisting cognitive decline in both preclinical models and patients. However, single mild TBI, the most frequent form of brain trauma increases cerebral generation of reactive oxygen species (ROS) only transiently. We hypothesized, that co-morbid conditions may exacerbate long term ROS generation in cerebral arteries after mTBI. Since hypertension is the most important cerebrovascular risk factor in populations prone to mild brain trauma, we induced mTBI in normotensive and spontaneously hypertensive rats (SHR) and assessed changes in cytoplasmic and mitochondrial superoxide (O2-) production by confocal microscopy in isolated middle cerebral arteries (MCA) two weeks after mTBI using dihydroethidine (DHE) and the mitochondria-targeted redox sensitive fluorescent indicator dye MitoSox. We found that mTBI induced a significant increase in long term cytoplasmic and mitochondrial O2- production in MCAs of SHRs and increased expression of the NADPH oxidase subunit Nox4, which were reversed to the normal level by treating the animals with the cell-permeable, mitochondria-targeted antioxidant peptide SS-31(5.7 mg kg-1 day-1 , i.p.). Persistent mTBI-induced oxidative stress in MCAs of SHRs was significantly decreased by inhibiting vascular NADPH oxidase (apocyinin). We propose, that hypertension- and mTBI-induced cerebrovascular oxidative stress likely lead to persistent dysregulation of CBF and cognitive dysfunction, which might be reversed by SS-31 treatment.
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2020-04-05 15:42